Anales de la RANM

32 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 S U P L E M E N T O III SIMPOSIO · JÓVENES INVESTIGADORES Libro de Abstracts An RANM. 2024;141(02).supl01: 32 - 40      Rafael Romero-Becerra 1 , Ana Belén Alonso-Aguado 2 , Alba C. Arcones 2 , Juan Antonio Lopez 1,3 , Alfonso Mora 2 , Alessia Ferrarini 1 , Estefanía Nuñez 1 , Ivana Nikolic 1 , Luis Leiva-Vega 2 , Maria Elena Rodríguez 2 , Marta León 2 , Nuria Matesanz 1 , Jorge-Luis Tor- res 4,5 , Lourdes Hernández-Cosido 6,7 , Juan Carlos Silla-Castro 1 , Francisco González-Romero 8 , Patricia Aspichueta 8,9 , Fátima Sanchez-Cabo 1 , Miguel Mar- cos 6,7 , Valentín Fuster 1 , Jesús Vázquez 1,3 y Guadalupe Sabio 2 1. Centro Nacional de Investigaciones Cardivasculares (CNIC), Madrid, Spain 2. Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain 3. CIBER de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain 4. University Hospital of Salamanca-SACYL-IBSAL, Sala- manca, Spain derivada de paciente. La metodología para aislar las EVs tiene un gran impacto en los resultados, remarcando la importancia de una caracterización exhaustiva de las EVs. El ensayo de inmunomarcaje y el estudio proteómico confirman la presencia de EVs en nuestras muestras.     Alba C. Arcones 1 , Ana Belén Alonso-Aguado 1 , Marta León 1 , Elena Rodríguez 1 , Luis Leiva-Vega 1 , Cintia Folguiera 2 , María I. Cuartero 2,3 , Alicia García- Culebras 2,3 , Jorge Hernández Matarazzo 2 , María Ángeles Moro 2 , Guadalupe Sabio 1 1. Centro Nacional de Investigaciones Oncológicas, Ma- drid, España 2. Centro Nacional de Investigaciones Cardiovasculares, Madrid, España 3. Universidad Complutense de Madrid, Madrid, España Introduction In an increasingly aged and obese population, diseases such as diabetes, cancer cardiovascular and neurodegenerative diseases are on the rise. Recently, a positive correlation between obesity and cognitive decline and neurodegenerative diseases has been described, offering a new therapeutic target. Among the altered pathways found in obesity, chronic-low grade inflammation stands out for its relevance, since activation of microglia under obesogenic conditions is known to contribute both to the peripheral and central changes in metabolism and cognition. In this project, we set out to explore the metabolic and central consequences of preventing the activa- tion of nutritional stress-related pathways specifi- cally in microglia in conditions of dietary fatty acids and sugar overload. Methods Immortalized microglial BV2 cells were treated with a mixture of glucose, fructose and palmitate to mimic the dietary insults caused by a fatty acids and sugar overload; and used to characterize the mechanisms leading to aberrant microglial activation. Functional consequences of this pathological microglial activa- tion were assessed in vivo feeding High Fat-High Fructose (HFHF) diet to mice specifically depleting in microglia the nutritional stress pathway. Results Under chronic dietary insults, microglia specifi- cally activate the nutritional stress response cascade, both in vitro and in vivo. Blunting the activation of this pathway in mice prevents the body weight gain and increased adiposity observed in their control littermates when fed HFHF diet. This protection seems to be due to microglial-mediated increase in energy expenditure, in the absence of differences in overall body temperature, locomotor activity and food intake, or peripheral glucose homeos- tasis. Microglial BV2 cells inhibited for nutritional stress response activation preserve characteristics of resting microglia, with decreased proliferation and interleukin production, which could contribute to the metabolic protection conferred in vivo. Discussion Preventing the activation of nutritional stress pathways specifically in microglial cells might reduce its inflammatory status, helping protect relevant neuronal circuits implicated in the control of energy expenditure, memory and anxiety from the detrimental effects of dietary lipid and sugar overload. Thus, under obesogenic conditions, microglia could act as the link between peripheral alterations and changes in the brain. Funding ACA was funded by Juan de la Cierva-Formación, 2020; G.S. is a EMBO YIP member, received funding from the following programmes and organizations: MICIN-FEDER PID2022-138525OB-I00 2023- 26 funded by MICIU/AEI/10.13039/501100011033 and ERDF/UE; Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología IMPACT-2021. Instituto de Salud Carlos III., PDC2021-121147-I00.Convocatoria: Proyectos Prueba de Concepto 2021. Ministerio de Ciencia e Innovación.